Delayed apoptosis of tumor associated neutrophils in the absence of endogenous IFN‐β

The importance of neutrophils in tumor immune surveillance, invasive growth and angiogenesis becomes increasingly clear. Many of neutrophil activities are controlled by endogenous IFN‐β. Here, we provide evidence that endogenous IFN‐β is regulating the apoptosis of pro‐angiogenic tumor infiltrating neutrophils by influencing both, the extrinsic as well as the intrinsic apoptosis pathways. Accordingly, the life span of tumor associated neutrophils (TANs) is remarkably prolonged in tumor bearing Ifnb1−/− mice compared to wild type controls. Lower expression of Fas, reactive oxygen species, active Caspase 3 and 9, as well as a change in expression pattern of proapoptotic and antiapoptotic members of the Bcl‐2 family and the major apoptosome constituent Apaf‐1 is observed under such conditions. In line with inhibition of apoptosis and the prolonged neutrophil survival, in the absence of endogenous IFN‐β, a strong enhancement of G‐CSF expression and PI3 Kinase phosphorylation is detected. These data explain the increased longevity of tumor infiltrating neutrophils and the accumulation of such cells in tumors. Taken together, our findings add to the important role of Type I IFN in immune surveillance against cancer. What's new? While the importance of neutrophils in tumor angiogenesis, invasive growth, and immune surveillance is becoming increasingly clear, much still needs to be understood about the physiology of neutrophils. Here, the authors show that endogenous IFN‐β regulates the apoptosis of pro‐angiogenic tumor‐infiltrating neutrophils by influencing both the extrinsic and the intrinsic apoptosis pathways. These data offer an explanation for the increased longevity of tumor‐infiltrating neutrophils and the accumulation of such cells in tumors. Taken together, the findings provide further evidence for the important role of endogenous IFN‐β in immune surveillance against cancer and highlight the tremendous therapeutic potential of IFN‐β.